There are fundamentally three isohexides: isomannide, isoidide, and isosorbide. Isosorbide is a commercially-produced, bicyclic diol that is easily available from biological feedstock. Glucose can be hydrogenated to sorbitol. The latter, in turn, can be subjected to double dehydration so as to yield isosorbide. Its double hydroxyl function would make isosorbide of interest as a building block for polymerization. However, the making of polymers of suitable properties from isosorbide is hampered by the molecule's stereochemistry, since the two hydroxyl groups are directed to different sides of the molecule's plane. i.e., the up to now more easily obtainable isosorbide is unsymmetrical with one endohydroxyl group and one exo-hydroxyl group, resulting in asymmetrical reactivity and amorphous polymers (due to the lack of symmetry). Its epimer isomannide, which has two endo-hydroxyl groups, has proven to be unfavorable for polymerization due to low reactivity and low linearity. On the other hand, the epimer isoidide has two exo-hydroxyl groups, and has been viewed as far better suited for use as a building block for polymerization than either isosorbide or isomannide. The symmetrical structure of isoidide eliminates the regiochemical reactivity difference between the two hydroxyl functionalities.
Examples of polymers wherein isoidide would be suitably used as a building block include polyesters made by polycondensation of isoidide and a dicarboxylic acid or anhydride, and polycarbonates made by reaction with a bifunctional carboxyl compound such as phosgene. Isoidide would also be suitably used in other polymerizations wherein conventionally other diols are used. E.g., bisglycidyl ethers of isoidide can be used as a substitute for bisphenol-A in epoxy resins. Isoidide has also been used or proposed for use in place of petroleum-based monomers such as terephthalic acid, for instance. Exemplary processes for isoidide polymerization, particularly, semi-crystalline isoidide furanoate homopolyesters, are set forth in co-pending PCT Patent Application Publication No. WO2015166070 A1, published Nov. 5, 2015, “Polyisoidide Furanoate Thermoplastic Polyesters and Copolyesters.”
Isoidide, however, is not currently manufactured on a commercial scale, in part (but not exclusively) because of the high cost of the synthetic precursor iditol from which isoidide might be made by an analogous double dehydration pathway as employed for making isosorbide. Sorbitan isomers include 1,4-sorbitan monoanhydrohexitol (1,4-anhydrosorbitol), 3,6-anhydrosorbitol, 2,5-anhydrosorbitol, 1,5-anhydrosorbitol and 1,4,3,6-dianhydrosorbitol.
An alternative pathway to isoidide through the epimerization of isosorbide has been investigated as a way of getting around this difficulty, though the literature related to this alternative pathway is quite limited. In one recent publication, LeNotre et al. reported a highly efficient method for obtaining highly pure, resin-grade isoidide through catalytic epimerization of isosorbide using a ruthenium-on-carbon catalyst (LeNotre et al. “Synthesis of Isoidide through Epimerization of Isosorbide using Ruthenium on Carbon” ChemSusChem 6, 693-700, 2013). This reference shows the synthesis of isoidide from highly purified (>99.5% pure) isosorbide (Polysorb, Roquette, Lestrem, France).
Co-pending and commonly-assigned International Patent Application No. WO2013125950A1, filed Feb. 20, 2012 for “Method of making isoidide” (the “WO'950 application” or “WO′950”), such application being incorporated herein by reference in its entirety, is related and describes a process for the preparation of isoidide from isosorbide, wherein an aqueous solution of isosorbide is subjected to epimerization in the presence of hydrogen under the influence of a catalyst comprising ruthenium on a support, at a starting pH of above 7. WO′950 further provides a process for the preparation of isoidide from glucose by hydrogenating glucose to form sorbitol, dehydrating the resulting sorbitol to form isosorbide, then epimerizing the isosorbide into isoidide using a catalyst comprising carbon-supported ruthenium.
One challenge that this alternative pathway encounters is that the epimerization product exists as a mixture of three isohexides: isosorbide, isoidide and isomannide. The separation of these isomers has generally been by fractional distillation. While distillation is effective to a certain extent, the isohexides have relatively close boiling points at elevated temperatures and reduced pressures. This results in added cost and complexity. A related further challenge to the practical commercial fulfillment of this alternative pathway has been the difficulty, in light of the very high purities demanded by polymer manufacturers for monomer feedstocks, of producing a highly pure isosorbide feed to the epimerization process in the first place. The conversion of sorbitol to isosorbide by an acid-catalyzed double dehydration has been hampered by vexing side reactions in which unwanted by-products are formed; consequently, vigorous effort has been exerted (albeit largely for the purpose of producing and selling a monomer grade isosorbide rather than a monomer grade isoidide product) to develop methods whereby the side reactions are diminished. As taught by PCT Patent Application Publication WO0239957, published Sep. 6, 2002, a number of byproducts are formed during the production of isosorbide from sorbitol; conventional wisdom heretofore held that isosorbide must be separated from these before conversion to isoidide. These unwanted byproducts include, but are not limited to, monoanhydrides (notably 2,5-anhydro-D-mannitol; 2,5-anhydro-L-iditol; sorbitan (1,4-anhydro-D-glucitol); and 3,6-anhydro-D-glucitol), dimers of the monoanhydrides, and oligomeric compounds.
For example, in co-pending and commonly-assigned International Patent Application No. WO 2013138153, published Sep. 19, 2013 for “Process for making sugar and/or sugar alcohol dehydration products,” a process is disclosed for making one or more sugar dehydration products from an aqueous sugars solution including one or more of pentoses and hexoses. The aqueous sugars solution is subjected to an acid-catalyzed dehydration at an elevated temperature using a substituted sulfonic acid catalyst with low water solubility but which is solubilized in the aqueous sugars solution at the elevated temperature. Additionally, one or more dehydration products are made from an aqueous sugar alcohols solution including one or more of the alcohols from pentoses and hexoses, by subjecting the aqueous sugar alcohols solution to an acid-catalyzed dehydration at an elevated temperature using a substituted sulfonic acid catalyst with low water solubility but which is solubilized in the aqueous sugar alcohols solution at the elevated temperature.
In another background reference, co-pending and commonly-assigned International Patent Application No. WO 2014070371 A1, published May 8, 2014 for “Improved method of making internal dehydration products of sugar alcohols,” compositions having reduced color and/or color stable on storage under generally prevailing storage conditions, including isosorbide, are disclosed.
Another approach for managing color problems in isosorbide synthesis is disclosed in copending and commonly-assigned International Patent Application No. WO 2014070369 A1, published May 8, 2014 for “Hydrogenation of isohexide products for improved color.” This disclosure elucidates a process for making one or more isohexides, comprising dehydrating one or more hexitols in the presence of an acid catalyst to form a crude dehydration product mixture including one or more isohexides; further processing the crude dehydration product mixture to separate out one or more fractions of a greater purity or higher concentration of at least one of the isohexides in the crude dehydration product mixture and one or more fractions of a lesser purity or concentration; and hydrogenating at least one of: a) the crude dehydration product mixture; b) a neutralized crude dehydration product mixture, following a neutralization step performed on the crude dehydration product mixture; c) the product mixture following a neutralization step performed on the crude dehydration product mixture and further following a step conducted on the neutralized crude dehydration product mixture to remove ionic species therefrom; d) a greater purity or higher concentration fraction; and e) a lesser purity or concentration fraction, by reaction with a hydrogen source in the presence of a hydrogenation catalyst, under conditions effective to carry out hydrogenation. In addition, isosorbide is made by dehydrating sorbitol in the presence of an acid catalyst to form a crude isosorbide product mixture, hydrogenating the crude isosorbide product mixture by reaction with hydrogen in the presence of a hydrogenation catalyst, at a hydrogen pressure of at least about 6.9 MPa, and obtaining an isosorbide-enriched product from the hydrogenated crude isosorbide product mixture. Particularly, isosorbide is made by dehydrating sorbitol in the presence of an acid catalyst to form a crude isosorbide product mixture, removing ionic species from the crude isosorbide product mixture by contacting the crude isosorbide product mixture with one or more ion exchange resins, through ion exclusion means or through a combination of ion exchange and ion exclusion means, hydrogenating the crude isosorbide product mixture with ionic species having been removed therefrom, by reaction with hydrogen in the presence of a hydrogenation catalyst; and obtaining an isosorbide-enriched product with improved color from the hydrogenated crude isosorbide product mixture.
Similarly, copending and commonly-assigned International Patent Application Publication No. WO2014070370, published May 8, 2014 for “Additives for improved isohexide products” addresses the well-known color problem of isosorbide by dehydrating one or more hexitols in the presence of an acid catalyst to form a crude dehydration product mixture, adding one or more antioxidants to the crude dehydration product mixture, and further processing the crude dehydration product mixture containing the one or more antioxidants to yield a product enriched in one or more isohexides compared to the crude dehydration product mixture; the initial AHPA color of the isohexide-enriched products being 100 or less.
Enhanced yields of isosorbide and of the 1,4-sorbitan precursor of isosorbide were obtained in the acid-catalyzed dehydration of sugar alcohols in copending and commonly-assigned International Patent Application No. WO2014137619, Published Sep. 12, 2014 for “Process for acid dehydration of sugar alcohols.” These were obtained by acid-catalyzed dehydration of a sugar alcohol, comprising contacting the sugar alcohol with a water-tolerant Lewis acid catalyst at a temperature and for a time sufficient to produce water and at least a partially dehydrated sugar alcohol product. Specifically, isosorbide was produced from sorbitol by contacting sorbitol with an effective amount of homogeneous Lewis acid catalyst such as bismuth (III) triflate, gallium (III) triflate, scandium (III) triflate, aluminum triflate, indium (III) triflate, tin (II) triflate and combinations of two or more of these, at a temperature and for a time sufficient to produce a product mixture including isosorbide.
The color problem inherent in isosorbide synthesis has also been addressed in copending and commonly-assigned PCT Patent Application Publication No. WO2015112389A1, published Jul. 30, 2014 for “Process for producing isohexides”. Isohexides are continuously dehydrated in the presence of an acid catalyst under vacuum using a thin film evaporator to produce a crude dehydration product mixture including the isohexide dehydration product from the hexitol. Improved carbon accountability in the dehydration of sugar alcohols and carbon accountability levels greater that 75% have been achieved.
Judicious catalyst selection has enabled development of marked improvements in isosorbide yield, product accountability and color body retrenchment in copending and commonly-assigned International Patent Application Publication No. WO/2015/156846, published Oct. 15, 2015, for “Dehydration of a sugar alcohol with mixed combination of acid catalysts.”
Semi-crystalline polyesters from isoidide and 2,5-furandicarboxylic acid are disclosed in co-pending International Patent Application No. WO2015166070 A1, published Nov. 5, 2015, “Polyisoidide Furanoate Thermoplastic Polyesters and Copolyesters.” Semi-crystalline copolyesters from isoidide and a minor amount of either 1,4-butanediol or 2,3-butanediol with 2,5-furandicarboxylic acid are also taught, together with processes for making high molecular weight materials by melt polymerization providing a semi-crystalline polymer then performing solid state condensation on the semi-crystalline polymer.
However, as already mentioned above, polymer applications typically require pure monomer feedstocks. One skilled in the art considers it axiomatic that the properties of polymers produced from impure monomers are likely to be inadequate. Impurities in monomers can interfere with the process of polymerization. In addition, color precursors formed as by-products of the synthetic reactions can cause development of color problems in polymers made from isoidide.
In fact, sorbitans are the primary by-products in the isosorbide synthesis from sorbitol, causing significant problems with color development and isosorbide degradation over time. Sorbitans are very undesirable in isosorbide due to the detrimental effects their breakdown products exert on isosorbide. Sorbitans decompose readily in cascades of reactions to form a plurality of poorly-characterized product including furans; these further decompose to form compounds which discolor isosorbide and products produced therefrom. Sorbitans in isoidide are undesirable in most cases; the presence of sorbitan causes yellowing of crystalline isosorbide. Another known set of compounds formed in sorbitan decomposition cascades is organic acids. Organic acids react with isosorbide to break it down into other unwanted impurities, lowering isosorbide content as well. Previously mentioned International Patent Application No. WO 2014070371 A1 achieves the removal of sorbitans from sorbitol by distillation. Further, previously mentioned International Patent Application No. WO 2014070369 A1 cited Japanese patent application as teaching problems associated with the instability of sorbitans in isosorbide: “JP 2006/316025 for its part earlier indicated that the formation of degradation/decomposition products in aged samples of isosorbide was related to auto oxidation of the 1,4-sorbitan monoanhydrohexitol side product and to unspecified “side reactions” involving a solvent (such as water and organic solvents such as xylene and toluene) from the dehydration of sorbitol to make isosorbide. The JP'025 reference prescribes multiple distillations of the crude isosorbide in the absence of a solvent at gradually increasing temperatures and/or at least one such solventless distillation followed by thermal treatment of the isosorbide to reduce the 1,4-sorbitan content of the isosorbide product, with bleaching of the isosorbide product included in each case by treating with ion exchange resins and carbon adsorption.”
Perhaps not surprisingly, then, even when highly pure isosorbide is obtained and used in an epimerization process as described by Le Notre et al., a set of by-products are formed that with the isomannide and isosorbide epimers pose still further difficulties for obtaining the ultimately desired monomer grade purity isoidide product. International Patent Application No. WO 2013125950 (the WO'950 application) thus teaches in reference to Le Notre et al.'s proposed process that a method for making isoidide while avoiding side reactions is desirable. They point out that yield-reducing side reactions lead to undesirable mass loss, e.g. as a result of hydrodeoxygenation. The products of these side reactions included non-volatile hydrodeoxygenation (HDO) products. This follows the conventional wisdom that also dictates that side-reactions lead to unwanted by-products, thus reaction catalysts and reaction conditions must be cognizant of, if not focused on, minimizing by-products.
Conventional wisdom inherent in synthetic reactions dictates that side-reactions leading to unwanted by-products should be avoided from a yield-loss perspective. Conventional wisdom would also dictate, as observed previously, that in order to produce high-purity products, high purity starting materials are needed. Fundamental to multi-step reaction procedures is the tenet that the purity of the product of each step is proportional to the purity of the starting material or intermediate reacted in that step. Conventional wisdom also speaks to purification procedures, which should be optimized to give the starting materials and intermediates of high purity.
However, we have now discovered, contrary to these conventional paradigms, that when isoidide is made by epimerization of a starting isosorbide composition in which costly purification steps are skipped so that certain isosorbide reaction by-products have been allowed to remain from an isosorbide containing these certain isosorbide reaction by-products (hereafter, “isosorbide feedstock containing one or more sorbitans”)—nevertheless monomer grade-purity isoidide may be made therefrom in unexpectedly good yields.
Independently we have determined that the epimerization of an epimerization reactor feed containing one or more sorbitans, such as an incompletely purified feed mixture, enables certain economies in the downstream separation and purification measures that are needed to produce monomer grade isoidide (where “monomer grade isoidide” is understood herein as an isoidide of at least 99.5 percent purity, while preferably the purity obtained is 99.9 percent or better), in addition to the just-mentioned economies in the upstream generation of an isosorbide feedstock for epimerization.
The great bulk of the literature related to isohexide purification technologies has been developed, again not surprisingly, in the context of the purification of product mixtures from the double dehydration of hexitols. In regard to the production of isosorbide from sorbitol, these product mixtures conventionally all contain isomannide, isosorbide and isoidide, as well as partially dehydrated sorbitans. Nevertheless, the isohexide purification art developed for the purification of hexitol double dehydration product mixtures does represent pertinent art for the task of purifying an epimerization product mixture as produced in an epimerization of isosorbide to provide isoidide.
As summarized in U.S. Pat. Nos. 7,122,661 and 8,008,477, a number of approaches had been suggested previously (that is, previous to these two patents) for obtaining the internal dehydration products (and particularly for obtaining the dianhydrohexitols such as isosorbide especially) in greater purity, for a variety of reasons. Some of these approaches sought improvements in purity through changes to the dehydration process by which the dianhydrohexitols are made, while other approaches involved a form of purification after the dianhydrohexitol compositions are formed.
For example, British Patent No. GB 613,444 describes the production of an isosorbide composition through dehydration carried out in a water/xylene medium, followed by distillation and recrystallization from an alcohol/ether mixture.
International Patent Application No. WO 00/14081 describes distillation and recrystallization from a lower aliphatic alcohol, or distillation alone in the presence of sodium borohydride and in an inert atmosphere.
U.S. Pat. No. 4,408,061 uses gaseous hydrogen halide or liquid hydrogen fluoride dehydration catalysts with carboxylic acid co-catalysts followed by distillation of the crude isosorbide or isomannide compositions thus obtained.
U.S. Pat. No. 7,122,661 for its part describes a process for obtaining isohexide compositions of 99.5% or greater purity and improved storage stability, without necessarily involving a comparatively costly and low yielding post-distillation crystallization step from a solvent medium, through using an ion-exchange step followed by a decolorization treatment step. More particularly, a distilled isohexide composition is described as subjected to treatment with at least one ion-exchange means, which can be a mixed bed of anionic resin(s) and cationic resin(s) or a succession of cationic resin(s) and anionic resin(s), followed by treatment with at least one “decolorizing means”. The decolorizing means can be activated charcoal in granular or pulverulent form. In certain embodiments, a second treatment with the decolorizing means is contemplated before the ion-exchange treatment step.
In J. Amer. Chem. Soc. 67 1865 (Oct. 1945), a column of adsorptive clay was proposed for isohexide separation: “A mixture, in disproportionate amounts, of 1,4:3,6-dianhydrosorbitol (isosorbide), 1,4:3,6-dianhydro-D-mannitol (isomannide), and 1,4:3,6-dianhydro-L-iditol (isoidide) was chromatographed to show three zones.”
International Patent Application No. WO02/39957 developed a chromatographic approach, operable without heat, for removal of unwanted reaction by-product from isosorbide. To separate isohexides produced by an acid acid-catalyzed hydrolysis of sorbitol (approximate composition by weight of 75% isosorbide) from non-isohexides (10% anhydro by-products (hydrodeoxygenation (HDO) reaction products and 15% dimers/oligomers), they employed acid resins in the protonated (H+) form in simulated moving bed chromatography. However, their acid resins in the protonated form were not able to separate isomers/epimers such as isosorbide from isoidide, as evidenced by the isoidide content in their purified isosorbide, and were certainly not able to obtain a purified isoidide.
Distillation followed by crystallization would likely be the most favored approach, generally speaking, for purifying the isohexide product mixtures from the double dehydration of hexitols. Isoidide purification by crystallization is, however, poorly understood. Early attempts to crystallize a water solution of isoidide by evaporation afforded a syrup from which no crystalline material could be obtained. The completely benzoylated derivative could be fractionally crystallized to give pure isoidide dibenzoylate (Journal of the American Chemical Society (1946), 68, 939-41). Crystallization from solvent of the benzoic acid esters of isoidide was taught in U.S. Pat. No. 3,023,223 (issued Feb. 23, 1962), and benzoyl derivatives and nitrate derivatives were crystallized from solvents in U.S. Pat. No. 4,721,796 (issued Jan. 26, 1988), but isoidide was not crystallized in either patent. Anhydrous sugar alcohol was crystallized from ethanol (Abstracts, Japanese Patents No. JP5492497 and JP5492531, both issued May 14, 2014). An alternative approach is presented in International Patent Application No. WO 01/81785, published Jun. 21, 2012, which teaches the addition of a saccharide distillation aid to a reaction product of mixed anhydrosugar alcohols (isosorbide, isomannide, isoidide) followed by distillation, such as at 220° C. under a vacuum of 3 mm Hg. The saccharide reportedly increases the flow properties of the system; separation of isoidide from isosorbide was not taught. Distillation is also employed in International Patent Application No. WO 14/73843, published May 15, 2014 to obtain “anhydrosugar alcohol (in particular, isosorbide, isomannide, isoidide, and the like) having a purity of 98 percent or higher and containing less than 0.1 percent of sorbitol and a sorbitan isomer, which are impurities, in a high total distillation yield of 94 percent or higher.” This is accomplished by “distilling the converted liquid over two or more stages by sequentially using a combination of an external condenser type wiped film evaporator and an internal condenser type short path evaporator” (Abstract).